Tahiti’s pearl farming industry plays a major socio-economic role in French Polynesia. In an increasingly competitive market where the production of high quality pearls becomes essential, research can help secure and ensure sustainable production. In that context, Ifremer, in close collaboration with the “direction des resources marines” (French Polynesian government agency) has developed research projects on the “sustainable development of pearl farming”. This program is organized along 3 axes: (1) understanding the animal physiology and initiating a genetically selective breeding program of donor oysters; (2) understanding pearl oyster larvae dispersal and recruitment; (3) understanding the molecular mechanisms underlying biomineralization processes during shell and pearl formation. It is in this frame that we have developed a highthroughput Expressed Sequence Tags pyrosequencing program on the calcifying mantle, combined with proteomic analyses of the shell and pearl. We analyzed 276738 EST sequences, leading to the constitution of a P. margaritifera mantle transcripts catalogue of 82 sequences potentially involved in biomineralization. Our results provided direct evidence that our ESTs data set covers a large number of the matrix proteins of P. margaritifera. In addition, our proteomic analysis enabled us to retrieve, in silico, all the sequences from P. margaritifera involved in the biomineralization process already published on databases. Integration of these two methods allowed, for the first time, the global composition of calcifying tissue and calcified structures to be examined in tandem.